The present proposal contains three separate research questions with a different background that both will be an extension of the Wheezing Illnesses Study Leidsche Rijn (WHISTLER).
Study 1: The relations between early childhood obesity and arterial disease.
Study 2: Low lung function in early childhood: nature or nurture?
Study 3: The relation between Diabetes type I during pregnancy and vascular characteristics in the offspring.

Study 1: The prevalence of childhood overweight and obesity in the Western
population has reached epidemic proportions and is continuing to increase. In
addition, the likelihood that an obese child will remain obese into adulthood
is high. The increase in obesity prevalence, particularly among younger age
groups, is likely to have long-term implications for cardiovascular disease in
the years to come. The age at which excess weight begins to exert its toll on
the cardiovascular system is still unknown, as is the exact mechanism through
which cardiovascular damage is accomplished. Obesity might adversely affect
cardiovascular health through associations with dyslipidemia, inflammation and
hypertension. Obesity might also impair vascular function by vasoactive
compounds such as leptin, produced by adipose tissue.

Study 2: At the age of 10 years children with asthma have worse lung function
in comparison to healthy controls and this difference persists until late
adulthood (so-called *tracking*). Until now, it is unclear whether this poor
lung function is due to decreased function from birth (i.e. probably *nature*-
factors play an important role) or to progressive loss of function secondary to
chronic inflammation and environmental factors (i.e. predominantly *nurture*-
factors are important) at very early age. We hypothesize that in healthy
children lung function tracks from birth over the first years of life but that
different early mechanical and environmental factors can substantially worsen
lung function (*de-tracking*).

Study 3: There is now a growing body of evidence that adult cardiovascular
disease may have its origin in early (fetal) life, when specific insults during
development may alter later body composition and metabolism. During diabetic
pregnancy, maternal hyperglycaemia induces fetal hyperglycaemia, which in turn
makes the developing tissues in the offspring more vulnerable to functional
alterations later in life. This may eventually lead to the development of some
of the components of the metabolic syndrome, such as obesity, hypertension and
impaired glucose tolerance. Therefore, it is important to recognize
cardiovascular disease risk factors early in the course of life and even, if
possible, already in childhood.

Study 1: The purpose of this study is to gain more insight in the
characteristics that are related to vascular damage at a young age, and
particularly to detect if obesity is related to vascular damage (and thus the
risk of cardiovascular disease in later life) in early childhood.

Study 2: The current proposal will answer 3 specific questions in a unique
birth cohort setting:
1. To what extent does neonatal lung function determine lung function over the
first years of life?
2. Are different asthma-phenotypes (resulting in different periods of lung
stress) associated with changes in lung function over the first years of life?
3. Do environmental factors affect development of lung function over the first
years of life?

Study 3:To investigate whether children born from mothers with Diabetes type I,
are more vulnerable to vascular changes.

The study that we propose to answer the research questions of parts 1 and 2 is
a cross-section among preschool children who took part in a birth cohort. Study
3 is a cross-sectional design.

There's no risk for the participants.